Yan Huan, Zeng Liang, Zhang Yongchang
Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China.
Heliyon. 2024 Apr 22;10(9):e29928. doi: 10.1016/j.heliyon.2024.e29928. eCollection 2024 May 15.
Patients with non-small cell lung cancer (NSCLC) and anaplastic lymphoma kinase (ALK) mutations have previously derived substantial benefits from ALK tyrosine kinase inhibitors (ALK-TKIs). However, resistance may develop in some patients. We present a case of co-mutation with anaplastic lymphoma kinase (ALK) and rearranged during transfection (RET)-rearranged NSCLC, representing a novel resistance mechanism to ALK-TKIs, in which the patient exhibited a favorable response to combination therapy with ensartinib and pralsetinib. Notably, the patient survived 12 months without experiencing adverse events, a rare occurrence in ALK-rearranged lung adenocarcinoma cases. This case provides further evidence for the existence of RET rearrangements in ALK-positive lung cancer and their potential treatment response to a combination of ALK inhibitors and pralsetinib. This case underscores that a dual-target therapy involving ALK inhibitors, specifically ensartinib and pralsetinib, could be a viable approach in cases of RET-rearranged lung cancer with concurrent targetable ALK mutations. We propose the consideration of this dual-target approach, specifically employing ensartinib and pralsetinib, in managing RET-rearranged lung cancer coexisting with targetable ALK mutations. Given the potential efficacy of these treatments, it is imperative to proactively conduct molecular profiling tests in NSCLC patients upon the emergence of resistance.
非小细胞肺癌（NSCLC）且具有间变性淋巴瘤激酶（ALK）突变的患者此前已从ALK酪氨酸激酶抑制剂（ALK-TKIs）中获得了显著益处。然而，部分患者可能会产生耐药性。我们报告了一例ALK与转染重排（RET）重排的NSCLC共突变病例，这代表了一种对ALK-TKIs的新耐药机制，该患者对恩沙替尼和普拉替尼联合治疗表现出良好反应。值得注意的是，该患者存活了12个月且未出现不良事件，这在ALK重排的肺腺癌病例中较为罕见。该病例为ALK阳性肺癌中RET重排的存在及其对ALK抑制剂和普拉替尼联合治疗的潜在反应提供了进一步证据。该病例强调，对于伴有可靶向ALK突变的RET重排肺癌病例，涉及ALK抑制剂（特别是恩沙替尼和普拉替尼）的双靶点治疗可能是一种可行的方法。我们建议在处理与可靶向ALK突变共存的RET重排肺癌时考虑这种双靶点方法，特别是使用恩沙替尼和普拉替尼。鉴于这些治疗的潜在疗效，在NSCLC患者出现耐药时积极进行分子谱检测至关重要。
